Editing 1430: Proteins
Warning: You are not logged in. Your IP address will be publicly visible if you make any edits. If you log in or create an account, your edits will be attributed to your username, along with other benefits.
The edit can be undone.
Please check the comparison below to verify that this is what you want to do, and then save the changes below to finish undoing the edit.
| Latest revision | Your text | ||
| Line 12: | Line 12: | ||
{{w|Protein folding}} is the process by which proteins, which are floppy, unstructured chains of {{w|amino acids}} when initially synthesized in a cell, assume a stable, functional shape. If the folding process does not complete, or completes incorrectly, the resulting protein can be inactive or even toxic to the body. Misfolded proteins are responsible for several {{w|neurodegenerative}} diseases, including {{w|Alzheimer's disease}}, {{w|amyotrophic lateral sclerosis}} (ALS), and {{w|Parkinson's disease}}, as well as some non-neurodegenerative diseases such as cardiac amyloidosis. | {{w|Protein folding}} is the process by which proteins, which are floppy, unstructured chains of {{w|amino acids}} when initially synthesized in a cell, assume a stable, functional shape. If the folding process does not complete, or completes incorrectly, the resulting protein can be inactive or even toxic to the body. Misfolded proteins are responsible for several {{w|neurodegenerative}} diseases, including {{w|Alzheimer's disease}}, {{w|amyotrophic lateral sclerosis}} (ALS), and {{w|Parkinson's disease}}, as well as some non-neurodegenerative diseases such as cardiac amyloidosis. | ||
| − | Cueball asks Megan | + | Cueball asks Megan why it is such a hard computational problem; Megan's response is to ask Cueball if he's ever {{w|Origami|folded paper}} to make a {{w|Crane (bird)|crane}}. When he responds in the affirmative, she then compares the problem of predicting protein folding to creating a ''living'' crane by the paper-folding process. The analogy is that a protein cannot just fold to a figurative representation of a bio-molecule, the way a paper crane superficially resembles a live crane; the protein must assume an exact, perfect fold in order to be functional. |
| − | + | {{w|Levinthal's paradox}} is a thought experiment, also constituting a self-reference in the theory of protein folding. In 1969, Cyrus Levinthal noted that, because of the very large number of degrees of freedom in an unfolded polypeptide chain, the molecule has an astronomical number of possible conformations. For example, a polypeptide of 100 {{w|Residue (chemistry)|residue}}s will have 99 peptide bonds, and therefore 198 different {{w|Dihedral angle|phi and psi bond angles}}. If each of these bond angles can be in one of three stable conformations, the protein may misfold into a maximum of 3<sup>198</sup> different conformations (including any possible folding redundancy). Therefore, if a protein were to attain its correctly folded configuration by sequentially sampling all the possible conformations, it would require a time longer than the age of the universe to arrive at its correct native conformation. This is true even if conformations are sampled at rapid (nanosecond or picosecond) rates. The "paradox" is that most small proteins fold spontaneously on a millisecond or even microsecond time scale. This paradox is central to computational approaches to protein structure prediction. | |
| − | + | As Cueball mentally turns over the hypothetical process of folding paper to make a living crane, he wonders if he is allowed to perhaps "cut" the paper to make more complicated folds available. In origami, purists [http://www.barf.cc/jeremy/origami/BOOK/essays/origami_purism/origami_purism.htm] considered it as cheating if you cut the paper or use more than one sheet of paper, which is why Cueball asked if he was 'allowed' to do such in the hypothetical exercise they are discussing. | |
| − | |||
| − | As Cueball mentally turns over the hypothetical process of folding paper to make a living crane, he wonders if he is allowed to perhaps "cut" the paper to make more complicated folds available. In origami, purists [ | ||
Megan replies "if you can fold a Protease enzyme;" these are proteins whose job it is to break down (i.e. "cut") other proteins, often in very specific ways. In this manner, Protease enzymes are analogous to extremely specialized scissors, so Megan is effectively saying "You can make cuts if you can fold yourself a pair of scissors." Of course, when trying to predict the folding trajectory in nature of a protein A, and one is allowed to make cuts during the process, one is making the assumption that the Protease that cut protein A is already folded and functional. In other words, making cuts while folding might actually make the process ''more'' complicated, not less, as now you have to consider how the cutting enzyme is folded, too. | Megan replies "if you can fold a Protease enzyme;" these are proteins whose job it is to break down (i.e. "cut") other proteins, often in very specific ways. In this manner, Protease enzymes are analogous to extremely specialized scissors, so Megan is effectively saying "You can make cuts if you can fold yourself a pair of scissors." Of course, when trying to predict the folding trajectory in nature of a protein A, and one is allowed to make cuts during the process, one is making the assumption that the Protease that cut protein A is already folded and functional. In other words, making cuts while folding might actually make the process ''more'' complicated, not less, as now you have to consider how the cutting enzyme is folded, too. | ||
